Multi-stroke delivery pumping mechanism for a drug delivery device for high pressure injections

ABSTRACT

A dual-chambered drug delivery device ( 201 ) includes a cartridge ( 211 ) having a first chamber ( 212 ) for storing a medicament and a second chamber ( 211 ) in fluid communication with the first chamber ( 212 ). A dose setting member ( 241 ) is used to set a medicament dose to be injected at an injection site. A piston ( 281 ) is disposed in the second chamber ( 221 ). An upward stroke of the piston ( 281 ) draw a portion of the medicament dose into the second chamber ( 221 ) and a downward stroke of the piston ( 281 ) expels the portion of the medicament dose. A needle ( 205 ) communicates with the second chamber ( 221 ) for sequentially injecting the portions of the medicament dose into the injection site.

CROSS REFERENCE TO RELATED APPLICATION

This application claims the benefit under 35 U.S.C. §119(e) of U.S.Provisional Application Ser. No. 61/193,594, filed Dec. 9, 2008, theentire content of which is hereby incorporated by reference.

FIELD OF THE INVENTION

The present invention relates generally to a drug delivery device thatfacilitates high pressure medication injections. More particularly, thepresent invention relates to a drug delivery device that diverts highpressures away from the original drug container to prevent medicamentleakage and inaccurate doses. Still more particularly, the presentinvention relates to injecting medication in small packets or pulses insuccession to lower the force required to inject a medicament doseintradermally.

BACKGROUND OF THE INVENTION

Insulin and other injectable medications are commonly given withsyringes into the intradermal layer of the skin and other dense tissues.Intradermal medication injections result in faster uptake of themedication, thereby resulting in improved therapy. Such injectionsrequire higher injection pressures, upwards of 200 psi, than traditionalsubcutaneous injections.

Techniques and devices are known for administering an injection into theintradermal region of the skin. One method, commonly referred to as theMantoux technique, uses a “standard” needle and syringe, i.e., a syringetypically used to administer intramuscular or subcutaneous injections.The health care provider administering the injection follows a specificprocedure that requires a somewhat precise orientation of the syringewith regard to the patient's skin as the injection is administered. Thehealth care provider must also attempt to precisely control thepenetration depth of the needle into the patient's skin to ensure thatit does not penetrate beyond the intradermal region. Such a technique iscomplicated, difficult to administer, and often may only be administeredby an experienced health care professional.

A conventional syringe 101 is shown in FIG. 1. The needle 103 issufficiently long to deliver the drug to the subcutaneous region of theskin. However, a user would not be able to easily deliver the drug tothe intradermal region of the skin, as discussed above.

Existing drug delivery pens offer several advantages over syringe-basedsystems for delivering insulin subcutaneously. Reusable drug deliverypens hold 20 or more doses without requiring the drug cartridge to berefilled. Dose setting is achieved simply with the use of a dial.However, those injection systems are designed for low pressuresubcutaneous injections. Intradermal injection of insulin and othermedications provides faster uptake of the drug, thereby leading toimproved therapy. Existing drug delivery pens have several limitationsregarding intradermal drug delivery. First, the mechanical advantageprovided by the pen is minimal and requires the user to supply upwardsof 20 lbs of force to generate sufficient pressure. Second, the pencomponents can be damaged by this high force, resulting in leaking andinaccuracy at the high pressures.

Drug delivery pens, such as the exemplary drug delivery pen 100 shown inFIGS. 2 and 3, are designed for intradermal injections and typicallycomprise a dose knob/button 24, an outer sleeve 13, and a cap 21. Thedose knob/button 24 allows a user to set the dosage of medication to beinjected. The outer sleeve 13 is gripped by the user when injectingmedication. The cap 21 is used by the user to securely hold the drugdelivery pen 100 in a shirt pocket, purse or other suitable location andprovide cover/protection from accidental needle injury.

FIG. 3 is an exploded view of the drug delivery pen 100 of FIG. 2. Thedose knob/button 24 has a dual purpose and is used both to set thedosage of the medication to be injected and to inject the dosedmedicament via the leadscrew 7 and stopper 15 through the medicamentcartridge 12, which is attached to the drug delivery pen through a lowerhousing 17. In standard drug delivery pens, the dosing and deliverymechanisms are all found within the outer sleeve 13 and are notdescribed in greater detail here as they are understood by thoseknowledgeable of the prior art. The distal movement of the plunger orstopper 15 within the medicament cartridge 12 causes medication to beforced into the needle 11 of the hub 20. The medicament cartridge 12 issealed by septum 16, which is punctured by a septum penetrating needlecannula 18 located within the hub 20. The hub 20 is preferably screwedonto the lower housing 17, although other attachment means can be used,such as attaching to the cartridge. To protect a user, or anyone whohandles the pen injection device 100, an outer cover 69, which attachesto the hub 20, covers the hub. An inner shield 59 covers the patientneedle 11 within the outer cover 69. The inner shield 59 can be securedto the hub 20 to cover the patient needle by any suitable means, such asan interference fit or a snap fit. The outer cover 69 and the innershield 59 are removed prior to use. The cap 21 fits snugly against outersleeve 13 to allow a user to securely carry the drug delivery pen 100.

The medicament cartridge 12 is typically a glass tube sealed at one endwith the septum 16 and sealed at the other end with the stopper 15. Theseptum 16 is pierceable by a septum penetrating cannula 18 in the hub20, but does not move with respect to the medicament cartridge 12. Thestopper 15 is axially displaceable within the medicament cartridge 12while maintaining a fluid tight seal.

The backpressure in subcutaneous injections is not very large, while thebackpressure associated with intradermal injections may be many timesgreater than that of subcutaneous injections. Existing drug deliverypens require a large force to inject medication into the intradermallayer, thereby making the intradermal medication injection difficult.For example, the backpressure often exceeds 200 psi for an intradermalinjection, while the backpressure for a subcutaneous injection isgenerally in the range of 30-50 psi. Thus, a need exists for a drugdelivery pen that provides a mechanical advantage to facilitate aninjecting a medicament dose intradermally. Furthermore, the drugdelivery pen components can be damaged due to the high pressuresassociated with intradermal injections, thereby resulting in medicationleakage and dose inaccuracy.

SUMMARY OF THE INVENTION

In accordance with an aspect of the present invention, a drug deliverydevice is provided that facilitates injecting insulin or othermedicaments at high pressures.

In accordance with another aspect of the present invention, a drugdelivery device has a secondary chamber that amplifies the injectionforce, thereby facilitating intradermal medication injections.

In accordance with yet another aspect of the present invention, highpressures associated with intradermal injections are diverted from theoriginal medication container to prevent medication leakage andinaccurate doses.

In accordance with another aspect of the present invention, a drugdelivery device is compact, thereby increasing usability andportability.

In accordance with another aspect of the present invention, a drugdelivery device injects the medicament in small packets or pulses insuccession to reduce the amount of pressure required to inject into anintradermal space.

In an exemplary embodiment of the present invention, the drug deliverydevice injects a medicament dose, such as insulin, at high pressures.The drug delivery device transports a user-determined bolus of themedicament from a primary container (or cartridge) to a secondarychamber using a fluid channel and a compression spring that provides aforce on the cartridge stopper, thereby resulting in a positive pressuredifferential between the cartridge and the secondary chamber. Thispositive pressure ensures the filling of the secondary chamber, therebyallowing for the proper operation of the pumping system. A vacuum is notrequired in the secondary chamber during the pumping action, therebypreventing bubble creation in the medicament dose. The bolus is set bythe user using a dial to select the desired medicament dose. The dialadvances a lead screw that activates the pumping system once theinjection is activated by a manual depression of the lead screw. Thepumping system moves fluid in predefined packet volume of approximately10 μl (1 unit of insulin) into the secondary chamber before injectingthe fluid (medicament) into the patient. This is accomplished using ascrew, nut, gear and cam set. The pumping action is repeated in packetsize intervals until the set bolus is completely injected. The secondarychamber employs a smaller cross sectional area than the primary(original) medication container to amplify injection pressure at a giveninput force.

Objects, advantages, and salient features of the invention will becomeapparent from the following detailed description, which, taken inconjunction with the annexed drawings, discloses exemplary embodimentsof the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

The above benefits and other advantages of the various embodiments ofthe present invention will be more apparent from the following detaileddescription of exemplary embodiments of the present invention and fromthe accompanying drawing figures, in which:

FIG. 1 is a front elevational view of a syringe;

FIG. 2 is a perspective view of a drug delivery pen;

FIG. 3 is an exploded perspective view of the drug delivery pen of FIG.2;

FIG. 4 is a perspective view of a drug delivery device according to afirst exemplary embodiment of the present invention;

FIG. 5 is a perspective view in cross section of the drug deliverydevice of FIG. 4;

FIG. 6 is a partial front elevational view in cross section of the drugdelivery device of FIG. 4;

FIG. 7 is a perspective view in cross section of a drug delivery deviceaccording to a second exemplary embodiment of the present invention;

FIG. 8 is a perspective view in cross section of the drug deliverydevice of FIG. 7;

FIG. 9 is a partial perspective view in cross section of the drugdelivery device of FIG. 7 showing the flexible rack;

FIGS. 9A and 9B are schematics of a valve system for a second chamber ofthe drug delivery device;

FIGS. 10A-10E are perspective view of a drug delivery device accordingto a third exemplary embodiment of the present invention;

FIGS. 11-14 illustrate priming and pressurization of the cartridge ofthe drug delivery device of FIG. 10;

FIGS. 15-20 illustrate the dose setting operation of the drug deliverydevice of FIG. 10;

FIGS. 21-25 illustrate delivering the dose with the drug delivery deviceof FIG. 10;

FIGS. 26-34 illustrate the dose tracking operation of the drug deliverydevice of FIG. 10.

Throughout the drawings, like reference numbers will be understood torefer to like parts, components and structures.

DETAILED DESCRIPTION OF THE EXEMPLARY EMBODIMENTS

The drug delivery device according to exemplary embodiments of thepresent invention allows the user to inject a medicament dose at highpressures with lower input forces by decoupling the first chamber of aprimary (original) medicament container and its cross sectional areafrom the injection mechanics.

Injecting a medicament dose in small packets or pulses, such as 10 μL,in succession, instead of at higher volumes can reduce the amount ofpressure required for an intradermal injection. Reducing the pressurecan result in less tissue damage and pain to the patient. Less pressurecan also result in a lower required user force to intradermally injectthe medication. Additionally, injecting a medicament dose in small dosesor packets can provide improved dose accuracy over existing drugdelivery pens, particularly at low dose ranges.

The presently disclosed drug delivery device has advantages in doseaccuracy and medication leakage over existing drug delivery pens bydiverting the high pressures associated with an intradermal injectionaway from the original drug container, particularly the stopper of theprimary cartridge. At high pressures, the primary drug container stoppercan deform, which can change the delivery volume and result in doseinaccuracies. Additionally, when the stopper is allowed to equilibrateand return to its natural volume after the needle is removed from theintradermal space and the back pressure dissipates, unwanted expulsionof the drug can occur.

In an exemplary embodiment of the present invention shown in FIGS. 4-6,a drug delivery device 201 injects a medicament, such as insulin, athigh pressures. A needle hub 203 is threadably connected to a housing202. A needle 203 is rigidly fixed in the needle hub 203 and is incommunication with the second chamber 221. Preferably, the needle 202 isan intradermal needle. Alternatively, the needle may be a subcutaneousneedle. Preferably, the needle is a small gauge needle, such as a 34gauge needle. The drug delivery device according to exemplaryembodiments of the present invention injects insulin, high viscositymedicaments, or other medicaments at high pressures.

The drug delivery device 201 transports a user-determined bolus of themedicament from a first chamber 211 of a primary container (or cartridge212) to the second chamber 221 using a fluid channel 231 and acompression spring 213 that provides a force on the cartridge stopper214, thereby resulting in a positive pressure differential between thefirst chamber 211 and the second chamber 221. This positive pressureensures the filling of the second chamber 221, thereby allowing for theproper operation of the pumping system. A vacuum is not required and ispreferably not created in the second chamber 221 during the pumpingaction, thereby preventing bubble creation in the medicament dose. Thebolus is set by the user using a dial 241 to select a desired dose. Thedial 241 advances a lead screw that activates the pumping system oncethe injection is activated by a manual depression of the lead screw. Thepumping system moves fluid in a predefined packet volume ofapproximately 10 μl (1 unit of insulin) into the second chamber 211before then injecting the fluid (medicament dose) into the patient. Thisis accomplished using a screw, nut, gear and cam set. The pumping actionis repeated in packet size intervals until the set bolus is completelyinjected. The second chamber 221 employs a smaller cross sectional areathan the first chamber 211 of the cartridge to amplify injectionpressure at a given input force.

As shown in FIGS. 4-6, the injection pressure is decoupled from thefirst chamber 211 of the cartridge 212 by moving the fluid to a secondchamber 221 via a pumping cam system. The second chamber 221 has asmaller cross sectional area than the first chamber 211 of the cartridge212, thereby providing a higher pressure for the same user input force.Using the relationship of pressure, force and area, P=F/A, a chamberwith half the cross sectional area produces twice the injection pressureat a given input force.

The medicament dose is set by rotating a dose setting member, a dosesetting wheel 241 as shown in FIG. 4, which is connected to the drivescrew 251. Rotation of the dose setting wheel 241 to set the medicamentdose causes the drive screw 251 to move upwardly out of the housing 202from a first position (FIG. 5) to a second position (FIG. 21). A dosetracker nut 265 is disposed on the drive screw 251 and remainsstationary on the drive screw as it is being moved upwardly out of thehousing 202 as the medicament dose is being set. When the medicamentdose is being delivered, the drive screw 251 slides through the dosetracking nut 263 such that the dose tracking nut moves upwardly on thedrive screw. When the dose tracking nut 263 abuts the upper end 265 ofthe dose tracking housing 267, the drive screw 251 is prevented frombeing moved upwardly out of the housing 202 by the upper end 265 of thedose tracking housing 267, thereby preventing a further medicament dosefrom being set.

A bevel gear 261 is rotatably engaged with the dose setting wheel 241. Aclutch 271 separates the dose setting wheel 241 from the bevel gear 261when the dose is being set. The bevel gear 261 has a cam shaft 263connected to a piston 281. Rotation of the bevel gear 261 causes thepiston 281 to move up and down in a reciprocating motion with rotationof the cam shaft 263. Upward movement of the piston 281 draws a smallportion or packet of the medicament dose from the first chamber 211 intothe second chamber 221. The downward movement of the piston 281 expelsthe packet of the medicament dose in the second chamber 221 out throughthe needle 205.

When the medicament dose has been set, the button 253 at an end of thedrive screw 251 is pushed downwardly by the user to inject themedicament dose. As the drive screw 251 is moved downwardly through thehousing, the clutch 271 causes the dose setting wheel 241 to engage thebevel gear 261, thereby rotating the bevel gear. As the bevel gear 261rotates, the cam shaft 263 drives the piston 281 up and down in areciprocating manner, thereby injecting the medicament dose throughseveral smaller sequential packet medicament dose injections. The traveldistance of the drive screw 251 corresponds to a predetermined number ofsequential packets to be injected. The total number of sequentialmedicament dose packets injected corresponds to the set medicament dose,which is accomplished by a single movement of the drive screw 251 fromthe second position to the first position.

Preliminary animal studies have demonstrated that the size of aninjection bolus has an effect on the resulting injection back pressurewhen injecting into the intradermal space. Smaller doses producedreduced back pressure during intradermal injections than larger boluses.Injecting medicament using 1 unit (10 μL) pulses, the peak back pressurefor an intradermal injection (and hence the peak injection pressure thatmust be applied) may be reduced by reducing the amount of dermis thatmust yield during injection at any particular instant.

Improved dose accuracy and reduced “drooling” issues related tocartridge stopper effects under high pressure also result fromdecoupling the high injection pressure associated with an intradermalinjection from the first chamber 211 of the cartridge 212.

A lower pressure is maintained in the cartridge 211 by moving theinjection fluid into the second chamber 221 prior to an injection. Thisallows a high pressure injection to occur without causing high pressuresin the first chamber 211 of the cartridge 212. In most existing drugdelivery pens, the delivered medicament dose results from a lineardisplacement of a drive screw 7 (FIG. 3) that translates a given lengthdependent on the dialed bolus volume. The dialed bolus determines thestroke length of the injection. The user imparts a force on theinjection button and completes the stroke length of the injection. Theforce and stroke of the injection motion are translated into a torque.The torque is then used to drive the drive screw 7 (FIG. 3) linearlyforward. That type of system can produce medicament dose inaccuracies atthe low end of the dosing range as the relationship between the initialstroke and the final drive screw motion.

Alternatively, as shown in FIGS. 7-9, a drug delivery device 301according to a second exemplary embodiment of the present inventionemploys a full-rack 351 to drive a cam wheel 331. The full-rack 451 is acontinuous, non-ending rack. The basic functionality and underlyingtechnical principles of the drug delivery device 301 of the secondexemplary embodiment are substantially similar to the drug deliverydevice 201 of the first exemplary embodiment.

A cartridge 311 has a first chamber for storing a medicament. When thecartridge 311 is first inserted in the housing 307, the cartridge 311 isdisposed in a first position as shown in FIG. 7. A needle hub 305 isconnected to the housing 307 such that a needle 303 rigidly fixed to theneedle hub 305 is in communication with the second chamber 321.

In the first position, the cartridge 311 is separated from aseptum-piercing needle 314. A priming button 315 extends outwardly fromthe housing 307 when the cartridge 311 is in the first position. A userpushes the priming button 315 inwardly, thereby moving a spring housing316 sideways away from an obstruction, such that the compression spring312 is released. The compression spring 312 expands and engages astopper disposed in the cartridge 311. The force of the compressionspring 312 on the cartridge 311 moves the cartridge into the secondposition, as shown in FIG. 8, in which the septum-piercing needle 314pierces the septum of the cartridge 311. The movement of the cartridge311 to the second position pressurizes the cartridge 311.

A dose setting wheel 322 is rotated to set a medicament dose. Rotationof the dose setting wheel 322 moves an injection rod 323 upwardly adistance that corresponds to the medicament dose being set. Duringinjection, the rod 323 is depressed by the use, thereby engaging theclutch and turning the cam wheel 331. The rotation of the cam wheel 331drives the piston 341 in a reciprocating (pumping) motion, pushing thefluid out on the downstroke, and allowing the second chamber 321 to fillfrom the first chamber 313 of the pressurized cartridge 311 on theupstroke.

The cam wheel 341 has a cam gear 343 for engaging the rack 351. Downwardmovement of the injection rod 323 moves the rack 351 clockwise as shownin FIGS. 7-9. The clockwise rotation of the rack 351 causes the cam gear343 to rotate clockwise, which rotates the cam wheel 341 clockwise. Acam curve 345 disposed on the cam wheel 341 engages the piston, therebyreciprocatingly moving the piston 341.

The force of the piston down stoke closes a first valve, V₁, 391(located at the fluid inlet to the second chamber 321) during theinjection because the force to deflect the valve shoulder is less thanthe stopper friction, and then opens the first valve, V₁, 391 during theupstroke for filling of the second chamber 321. Any suitable valve maybe used. A schematic of the valve system is shown in FIGS. 9A and 9B.

A second valve, V₂, 393 (located at the fluid exit of the second chamber321) opens only during injection when the pressure in the second chamber321 is high enough to compress the second valve 393, thereby opening theseal and allowing fluid to travel to the needle 303.

The drug delivery devices according to the first and second exemplaryembodiments shown in FIGS. 4-9 have an integrated dose tracking systemthat prevents dose setting when the medicament volume is limited. Asshown in FIGS. 7-9, a full rack embodiment features a reusable rack 351that is mechanically triggered during its third cycle to effectivelytrack the dose and prevent dose setting as the first chamber 313 of thecartridge 311 is emptied.

The second chamber 321 has a smaller cross sectional area than thecartridge 31, thereby providing a higher pressure using the same userinput force. A standard 3.0 mL insulin cartridge has a diameter ofapproximately 9.7 mm, thereby resulting in a cross sectional area ofA=πr²=4.85²*3.14159=73.9 mm². In a preferred embodiment, the secondchamber 321 of the drug delivery device 301 has a diameter of 3.5 mmresulting in a cross sectional area of 1.75²*3.14159=9.62 mm². For agiven pressure, P, a force multiplication is achieved using thefollowing relationships: P=F₁/A₁, P=F₂/A₂. Therefore, F₁/A₁=F₂/A₂. Theforce multiplier M_(f), F₁/F₂ becomes the ratio of the areas, A₁/A₂,M_(f)=73.9/9.62=7.7, with an efficiency, η, of 100%.

Therefore, without taking friction in the system into account (η=100%),this preferred embodiment of the drug delivery device would requireapproximately seven (7) times less force to achieve the same injectionpressure as a device that applies force directly to the primary insulincontainer (cartridge).

Taking friction into account, however, the force multiplier is slightlyreduced. The drug delivery device according to the first exemplaryembodiment (FIGS. 4-6 with a nut/screw drive), features an efficiency ofabout 50-60%, which results in an injection pressure of about 100-120psi (M_(f)=3-3.5) for the preferred embodiment. The drug delivery deviceaccording to the second exemplary embodiment (FIGS. 7-9 with a fullrack), has a higher efficiency than the first exemplary embodiment andproduces an injection pressure of about 150-180 Psi (M_(f)=5-6) for thepreferred embodiment. This efficiency increase is due to the lowerfriction of the rack (FIGS. 7-9) when compared to the nut/screw drive(FIGS. 4-6).

A third exemplary embodiment of a dual-chambered drug delivery device401 of the present invention is shown in FIGS. 10-36. The drug deliverydevice 401 operates substantially similarly to the drug delivery device301 according to the second exemplary embodiment shown in FIGS. 7-9. Thedrug delivery device 401 allows priming and pressurization of thecartridge, setting the medicament dose, delivering the medicament dose,and tracking the dose. A needle hub 407 is connected to the devicehousing 403. A needle 408 is rigidly fixed to the needle hub 408 andcommunicates with a second chamber 421 to deliver a medicament dose.

FIGS. 11-14 illustrate the operation of cartridge priming andpressurization. When the drug delivery device 401 is shipped, acompression spring housing 402 sits on a ledge 414 of the device housing403, as shown in FIGS. 11 and 12. An end of a compression spring 413engages the compression spring housing 402. The other end of thecompression spring 413 engages an inner surface of the device housing403, such that the compression spring 413 is in a compressed position.Pushing a priming button 415 inwardly moves the spring housing 402 offthe ledge 414, as shown in FIGS. 13 and 14. The compression spring 413expands until the compression spring housing 402 engages the stopper 404within the cartridge 411. The force of the compression spring 413 on thecartridge stopper 404 causes the cartridge 411 to move from a firstposition shown in FIGS. 11 and 12 in which the cartridge septum 419 isseparated from the septum-piercing needle 417 to a second position shownin FIGS. 13 and 14 in which the septum-piercing needle 417 pierces thecartridge septum 419.

When the compression spring 413 is engaging the cartridge stopper 404and the septum-piercing needle 417 is piercing the cartridge septum 419,the cartridge 411 is primed and pressurized. Medicament stored in afirst chamber 406 of the cartridge 411 is now able to enter the fluidconduit 431. When a depleted cartridge 411 is removed from the housing403, insertion of the replacement cartridge 411 returns the primingbutton 415 to a position extending outwardly of the housing as shown inFIGS. 11 and 12.

FIGS. 15-20 illustrate setting a medicament dose with the drug deliverydevice 401. A dose setting wheel 441 has a gear 442 that engages teeth404 of the housing 403, as shown in FIGS. 15 and 16. Increasing the dosesetting with the dose setting wheel (rotating the dose setting wheelclockwise as shown in FIG. 15) clicks the ratchet teeth 443 and 444 overthe rack teeth 445, as shown in FIGS. 17 and 18, thereby moving the dosesetting wheel 441 upwardly in the housing groove 440 and the rack groove439. Upward movement of the dose setting wheel 441 moves the ratchet 453upwardly from a first position shown in FIG. 15 to a second positionshown in FIG. 21, such that a button 451 on an end of the ratchet isaccessible to the user outside of the housing 403.

To correct a medicament dose, the dose setting wheel 441 is rotatedcounter-clockwise as shown in FIG. 15. Dose correcting flexes theratchet teeth 443 and 444 outwardly such that the ratchet teeth 443 and444 disengage the rack teeth 445, thereby allowing the dose settingwheel 441 and ratchet 453 to move downwardly without moving the rack446, as shown in FIGS. 19 and 20. The ratchet 453 is fixed to the dosesetting wheel 441 such that the ratchet 453 and dose setting wheel 441move together.

FIGS. 21-25 illustrate the operation of delivering a medicament dose.The inject button 451 is connected to the ratchet 453, and the ratchetteeth 443 and 444 of the ratchet 453 engage the rack teeth 445 such thatdownward movement of the inject button 451 moves the rack 446downwardly. The downward movement of the rack 446 (clockwise rotation ofthe rack 446 as shown in FIG. 21) rotates cam gear 447, which in turnrotates the pump cam 461. The cam gear 447 is fixed to a cam wheel 461,which has a cam groove 463, as shown in FIG. 25. A first end of a camshaft 465 engages the cam groove 463 and a second end of the cam shaft465 is connected to a piston 471. As the cam shaft 465 travels along thecam groove 463 the piston is reciprocatingly moved up and down. Rotationof the cam wheel 461 causes reciprocal motion of the piston 471, asshown in FIGS. 24 and 25, thereby delivering the medicament dose in thesecond chamber 421. During the upstroke of the piston 471, a portion orpacket of the medicament dose is drawn from the first chamber 406 to thesecond chamber 421. During the downstroke of the piston, the medicamentdose packet is delivered from the second chamber 421 through the needle408 and into the skin at the injection site. When the ratchet 451 hasbeen completely reinserted into the housing 403, as shown in FIG. 10,the medicament dose has been fully injected over a sequence ofmedicament dose packets injected with each downstroke of the piston 471.

FIGS. 26-34 illustrate the dose tracking operation of the drug deliverydevice 401. The movable rack 446 has a carriage 448 disposed thereon. Asthe rack 446 moves, the carriage 448 moves closer to the ratchet teeth443 and 444, as shown in FIG. 26. Preferably, the rack 446 has asubstantially elliptical shape. The ratchet teeth 443 and 444 interferewith the carriage 448 when the first chamber 406 of the cartridge 411 isempty. When the carriage 448 contacts the ratchet teeth 443 and 444further medicament dose setting is prevented. For example, afterapproximately 2.5 rack revolutions (cartridge capacity) the carriage 448prevents further medicament dose setting.

As shown in FIGS. 27 and 28, a medicament dose is ready to be made (theratchet 453 has been moved outside of the housing 403). When thecarriage 448 is in this position, the first chamber 406 is full ofmedicament. A movable rack member 481 is initially in a first position,as shown in FIGS. 27 and 28, which is a down position and the sameposition as the remaining members of the rack 446. After the rack 446makes a first, full revolution, the movable rack member 481 rides up theramp 449 on the housing 403, as shown in FIGS. 29 and 30. The movablerack member 481 is now in a second, up position, which is above theremaining members of the rack 446. After the rack 446 makes a second,full revolution, the movable rack member 481 engages the carriage 448,as shown in FIGS. 31 and 32. The movable rack member 481 then pushes thecarriage 448 with the rack 446 with further movement of the rack 446.After approximately another half revolution, the carriage 448 engagesthe ratchet teeth 443 and 444, as shown in FIGS. 33 and 34, therebypreventing further dose setting.

Alternatively, the drug delivery device according to exemplaryembodiments of the present invention can be used as a reconstitutingdrug delivery system. The first chamber contains a diluent. The secondchamber, which can be removable/replaceable, contains a solid drug.Accordingly, the drug delivery device enables a reconstitution orresuspension system. The first chamber can store sufficient diluent formany injections, and the second chamber can store a solid drug for fewerinjections, such as one or two. Accordingly, the drug delivery deviceaccording to exemplary embodiments of the present invention can be usedas a reconstitution system, including as a reconstitution system forhigh pressure injections.

The foregoing embodiments and advantages are merely exemplary and arenot to be construed as limiting the scope of the present invention. Thedescription of exemplary embodiments of the present invention isintended to be illustrative, and not to limit the scope of the presentinvention. Various modifications, alternatives and variations will beapparent to those of ordinary skill in the art, and are intended to fallwithin the scope of the invention as defined in the appended claims andtheir equivalents.

The invention claimed is:
 1. A dual-chambered drug delivery device,comprising: a cartridge having a first chamber for storing a medicament;a second chamber in fluid communication with said first chamber, acenterline of said first chamber being substantially parallel to andoffset from a centerline of said second chamber; a rotating dose settingmember for rotatably setting a medicament dose to be injected at aninjection site, said dose setting member being mechanically decoupledfrom said first chamber and said dose setting member being disposedexternal to said second chamber; a piston disposed in said secondchamber, an upward stroke of said piston drawing a portion of themedicament dose into said second chamber and a downward stroke of saidpiston expelling the portion of the medicament dose; and a needlecommunicating with said second chamber for sequentially injectingportions of the medicament dose into the injection site.
 2. Thedual-chambered drug delivery device according to claim 1, wherein adrive screw is movably connected to said dose setting member such thatrotation of said dose setting member moves said drive screw upwardly. 3.The dual-chambered drug delivery device according to claim 2, wherein abevel gear is rotatably connected to said dose setting member such thatdownward movement of said drive screw rotates said dose setting member,which rotates said bevel gear; and a piston is movably connected to saidbevel gear.
 4. The dual-chambered drug delivery device according toclaim 3, wherein a clutch is connected to said dose setting member, saidclutch separating said dose setting member from said bevel gear when themedicament dose is being set and engaging said dose setting member andsaid bevel gear when said medicament dose is being delivered.
 5. Thedual-chambered drug delivery device according to claim 2, wherein a dosetracking nut is disposed on said drive screw to prevent furthermedicament doses from being set when the remaining medicament in saidfirst chamber is less than a predetermined amount.
 6. The dual-chambereddrug delivery device according to claim 1, wherein said dose settingmember mechanically drives a piston of only the second chamber of saidfirst and second chambers.
 7. The dual-chambered drug delivery deviceaccording to claim 1, wherein a centerline of said dose setting memberis coincident with the centerline of said second chamber.
 8. Thedual-chambered drug delivery device according to claim 1, wherein saidsecond chamber is disposed at a position below said first chamber.
 9. Amethod of injecting medicament using a dual-chambered drug deliverydevice, comprising the steps of: storing a medicament in a first chamberof a cartridge, a second chamber being in fluid communication with saidfirst chamber; setting a medicament dose by rotating a dose settingmember that is mechanically decoupled from said first chamber, acenterline of said first chamber being substantially parallel to andoffset from a centerline of said second chamber, and said dose settingmember being disposed external to said second chamber; transferring aportion of the medicament dose from the first chamber to the secondchamber via a piston disposed in said second chamber, an upward strokeof said piston drawing the portion of the medicament dose from saidfirst chamber into said second chamber and a downward stroke of saidpiston expelling the portion of the medicament dose; injecting theportion of the medicament dose from the second chamber into an injectionsite via a needle; and repeating the injecting of portions of themedicament dose until the entire medicament dose is injected.
 10. Themethod of injecting medicament using a dual-chambered drug deliverydevice according to claim 9, wherein the injecting of a portion of themedicament dose and the repeating thereof is accomplished by one strokeof an injection rod.
 11. The method of injecting medicament using adual-chambered drug delivery device according to claim 9, furthercomprising tracking the amount of the medicament stored in the firstchamber.
 12. The method of injecting medicament using a dual-chambereddrug delivery device according to claim 11, further comprisingpreventing the medicament dose from being set when the stored medicamentbeing tracked is less than a predetermined amount.